GTP depletion and other erythrocyte abnormalities in inherited PNP deficiency.
GTP levels were low and NAD+ levels high in purine nucleoside phosphorylase (PNP) deficient erythrocytes, in addition to the raised deoxy-GTP (dGTP) levels previously noted by others. dGTP was also identified in the PNP deficient child's lymphocytes. A further novel finding was the conversion of hypoxanthine to inosine by the PNP deficient red cells, as compared to inosine monophosphate (IMP) in controls. This has been attributed to IMP formation with subsequent breakdown, and raises interesting questions regarding the controls which normally maintain erythrocyte nucleotide pools. These findings may also explain the gross purine overproduction seen in this defect; they may likewise be related to the associated immunodeficiency, anaemia, and other clinical manifestations. The results may also have important implications for the development and clinical use of PNP inhibitors.
D000243:Adenosine Deaminase / Q000172:deficiency; D000255:Adenosine Triphosphate / Q000097:blood; D003570:Cytidine Triphosphate / Q000097:blood*; D003597:Cytosine Nucleotides / Q000097:blood*; D004912:Erythrocytes / Q000032:analysis*; D006801:Humans; D007042:Hypoxanthines / Q000378:metabolism; D007223:Infant; D008297:Male; D009243:NAD / Q000097:blood; D010430:Pentosyltransferases / Q000172:deficiency*; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency*
D003597:Cytosine Nucleotides; D007042:Hypoxanthines; D009243:NAD; D003570:Cytidine Triphosphate; D000255:Adenosine Triphosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D000243:Adenosine Deaminase